Image Guided Volumetrically Modulated Total Body Irradiation (TBI): Progress on Single Institution Phase 2 Clinical Trial
PURPOSE/OBJECTIVE(S): TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. MATERIALS/METHODS: Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% >= 90%, D98% >= 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant.
RESULT(S): Patients were treated to 12 Gy in 8 BID fractions (n=6) or 13.2 Gy in 8 BID fractions (n=3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2).
CONCLUSION(S): Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.
Assessing the reproducibility of CBCT-derived radiomics features using a novel three-dimensional printed phantom
PURPOSE/OBJECTIVE:Radiomics modeling is an exciting avenue for enhancing clinical decision making and personalized treatment. Radiation oncology patients often undergo routine imaging for position verification, particularly using LINAC-mounted cone beam computed tomography (CBCT). The wealth of imaging data collected in modern radiation therapy presents an ideal use case for radiomics modeling. Despite this, texture feature (TF) calculation can be limited by concerns over feature stability and reproducibility; in theory, this issue is compounded by the relatively poor image quality of CBCT, as well as variation of acquisition and reconstruction parameters. METHODS:In this study, we developed and validated a novel three-dimensional (3D) printed phantom for evaluating CBCT-based TF reliability. The phantom has a cylindrical shape (22Â cm diameter and 25.5Â cm height) with five inner inserts designed to hold custom-printed rods (1Â cm diameter and 10-20Â cm height) of various materials, infill shapes, and densities. TF reproducibility was evaluated across and within three LINACs from a single vendor using sets of three consecutive CBCT taken with the head, thorax, and pelvis clinical imaging protocols. PyRadiomics was used to extract a standard set of TFs from regions of interest centered on each rod. Two-way mixed effects absolute agreement intra-class correlation coefficient (ICC) was used to evaluate TF reproducibility, with features showing ICC values above 0.9 considered robust if their Bonferroni-corrected p-value was below 0.05. RESULTS:A total of 63, 87, and 83 features exhibited test-retest reliability for the head, thorax, and pelvis imaging protocols respectively. When assessing stability between discreet imaging sessions on the same LINAC, these numbers were reduced to 5, 63, and 70 features, respectively. The thorax and pelvis protocols maintained a rich candidate feature space in inter-LINAC analysis with 61 and 65 features, respectively, exceeding the ICC criteria. Crucially, no features were deemed reproducible when compared between protocols. CONCLUSIONS:We have developed a 3D phantom for consistent evaluation of TF stability and reproducibility. For LINACs from a single vendor, our study found a substantial number of features available for robust radiomics modeling from CBCT imaging. However, some features showed variations across LINACs. Studies involving CBCT-based radiomics must preselect features prior to their use in clinical-based models.
Evaluation of treatment plan uncertainties for vmat TBI [Meeting Abstract]
Purpose: To investigate the effect of patient positioning in Volumetric Modulated Arc Therapy (VMAT) for Total Body Irradiation (TBI) given the use of multiple isocenters, by simulating offsets in patient positioning and evaluating changes to planned dose distributions.
Method(s): VMAT treatment plans for seven TBI patients treated as part of a prospective stage II clinical trial were evaluated. Plan uncertainties were calculated by introducing 5mm and 10mm translational shifts to the plans' isocenters in the lateral (x), vertical (y), and longitudinal (z) directions. Dose distributions were then re-calculated in the treatment planning system (Eclipse), in order to evaluate dosimetric robustness to one global imaging shift at treatment. Differences in target volume (PTV) coverage and doses to organs at risk were evaluated based on four parameters: lung mean dose, PTV-V100%, PTV-D98%, and kidney mean doses.
Result(s): Lung mean dose increased an average of 8.2cGy, 4.4cGy, and 3.3cGy when shifted 5mm in the x, y, z directions (respectively) across seven patients; 33.2CGy, 18.5cGy, 18.3cGy for 10mm shifts in x, y, z. Target coverage V100% decreased an average of 0.3%, 0.03%, 0.1% for 5mm shifts, and 1.1%, 0.8%, 0.4% for 10mm shifts in x, y, z. D98% decreased 0.9%, 0.3%, 0.3% when shifted 5mm; 3.5%, 2.1%, 1.0% when shifted 10mm in x, y, z. Mean dose to the left kidney increased 6.6cGy, 9.7cGy, 2.8cGy for 5mm, and 28.1cGy, 32.7cGy, 18.0cGy for 10mm shifts in x, y, z. Right kidney mean dose increased 11.9cGy, 8.9cGy, 3.1cGy for 5mm, and 36.5, 30.5, 19.8cGy for 10mm.
Conclusion(s): Though small in relation to total dose, the largest increase in mean lung dose and decrease in coverage was seen with lateral shifts as compared to vertical or longitudinal shifts. These results support the use of an approach with preferential alignment to the chest region (lung-sparing), as long as residual imaging alignment outside the chest is kept below 10mm. Jose Teruel has received honorarium from Varian Medical Systems
Streamlining complex multi-isocentric VMAT based treatment delivery using a newly developed software tool [Meeting Abstract]
Purpose: Multi-isocentric treatment delivery for CSI and TBI poses specific challenges for treatment delivery. We have developed a software tool to streamline all aspects of delivery for therapists and physicists at the machine, as well as to inform attending physicians of setup variability and image residuals at different locations.
Method(s): Our institution delivers VMAT-based CSI and TBI with up to 3 and 7 isocenters, respectively. A software tool was developed to assist with treatment delivery including initial patient setup, patient imaging, automatic calculation of the optimal global shift based on each isocenter's ideal shift, and automatic calculation of each isocenter's couch coordinates. Initial treatment couch coordinates are queried via the Eclipse scripting API. The global shift was calculated prioritizing the head isocenter for CSI treatments and the chest isocenter for TBI treatments by first maximizing residual tolerance at any other location prior to accepting any residual deviation at these locations. Maximum residuals tolerance was determined based on target margins, plan uncertainty and as per physician instructions. Delivery parameters are reported to a document uploaded to ARIA via API.
Result(s): The developed tool was employed for 11 cases. The software tool replaced the need for plan shift comments or instructions for therapists. In particular, its use eliminated the need to provide isocenter shifts to therapists by directly providing final couch parameters for treatment, greatly reducing the risk of delivery errors. The software effectively informed the therapists if any expected tolerance was surpassed, triggering a patient setup evaluation.
Conclusion(s): The described software tool is a core component to our multi-isocenter treatment programs and has streamlined delivery of these complex techniques that would otherwise require complicated instructions, including multiple shifts and on-the-fly calculations of optimal image alignment based on multiple imaging locations. This has substantially reduced the possibility of delivery errors
Nyu clinical experience with total body irradiation: From 3d laterals to image-guided VMAT [Meeting Abstract]
Purpose: Patients receiving myeloablative total body irradiation (TBI) doses >= 12Gy are at risk of developing interstitial pneumonitis. At our institution, TBI transitioned from extended distance opposed Laterals to image-guided VMAT, in an effort to improve coverage while sparing lungs and kidneys. This work presents a dosimetric comparison between 3D Laterals and VMAT.
Method(s): Nine patients were treated with VMAT as part of an ongoing phase II single-arm clinical trial. VMAT patients were CT-simulated supine, with thermoplastic masks for head/neck, chest/abdomen/pelvis and feet. VMAT planning (12Gy (n=6) or 13.2Gy (n=3) in 8-BID fractions) utilizes 6MV multi-isocentric arcs and AP/PA beams to treat the upper and lower body, respectively. Ten 3D Lateral patients were CT-simulated supine with arms positioned/immobilized for lung shielding, with rice compensation between legs/feet. Laterals plan (12Gy in 8-BID fractions) uses 15MV, beam spoiler, head compensation, and subfields to maintain coverage and mean-lungs dose <10.5Gy. Target (Body-5mm, extending 3mm into lungs and kidneys for VMAT; Body-2cm for Laterals) coverage was evaluated at V100%, and D98% (percentage of Rx). Absolute dose to lungs and kidneys were reportedResults: Median Target V100% and D98% for VMAT was 93.2% (Range: 95.6% to 92.1%) and 90.2% (94.3% to 88.3%), whereas for Laterals V100% and D98% was 57.3% (66.5% to 46.3%) and 80.6% (75.5% to 84%). The median Lung mean dose was 7.6Gy (7.3Gy to 7.9Gy) for VMAT. The median mean dose to kidney was 10.4Gy (10.1Gy to 10.7Gy) for VMAT, and 12.5Gy (11.9Gy to 13.5Gy) for Laterals.
Conclusion(s): We have established a VMAT-TBI program for patients requiring myeloablative irradiation. Improvement in target coverage is demonstrated by V100% and D98%, while reducing the mean dose to the lungs significantly from 10.5Gy to 8Gy
Investigation into the relationship patient setup accuracy and in-vivo transit dosimetry for image-guided volumetrically modulated total body irradiation (TBI) [Meeting Abstract]
Purpose: In-vivo dosimetry for conventional total body irradiation (TBI) utilize point detectors placed along the patient surface to confirm the delivered dose matches prescription dose. However, in the volumetrically modulated arc therapy (VMAT) approach to TBI, the electronic portal imager device (EPID) can be utilized to acquire a 2-dimensional transmission fluence plane. This work explores the relationship between patient setup accuracy with transit in-vivo dosimetry.
Method(s): A total of 192 fields were investigated. Each VMAT plan consisted of four isocenters: head, chest, abdomen, and pelvis. Prior to treatment, the patient was imaged at the head, pelvis, and chest. Optimal couch shifts were determined for each isocenter under image guidance. The optimal IGRT shifts were determined using an inhouse application that minimized dose deviation using criteria established through plan uncertainty analysis performed in Eclipse. Translational couch residuals were recorded and defined as the difference in the global shift calculated and the optimal couch position with shifts. Transit dosimetry was measured per arc, and analyzed using SNC PerFRACTION with a gamma criteria of 10%/5mm, 5%/5mm, and 5%/7mm.
Result(s): Based on plan uncertainty analysis, clinical threshold for couch residuals were set to 7 mm (5 mm for chest isocenter) as there would be minimal impact on target coverage and organ sparing at those levels. Transit dosimetry showed that the average pass rate across all fields was 99.6%, 97.0%, and 99.2% for 10%/5mm, 5%/5mm, and 5%/7mm gamma criteria, respectively. Pearson correlation tests showed that there was weak correlation between gamma criteria and couch residuals. At stringent 3%/5mm gamma criteria, moderate correlation was found between lateral couch residuals for the head and chest and the head and chest arc analysis.
Conclusion(s): Transit dosimetry showed high pass rates using our couch residual tolerances, which confirmed the plan uncertainty analysis performed during treatment planning
Automatic treatment planning for VMAT-based total body irradiation using Eclipse scripting
The purpose of this work is to establish an automated approach for a multiple isocenter volumetric arc therapy (VMAT)-based TBI treatment planning approach. Five anonymized full-body CT imaging sets were used. A script was developed to automate and standardize the treatment planning process using the Varian Eclipse v15.6 Scripting API. The script generates two treatment plans: a head-first VMAT-based plan for upper body coverage using four isocenters and a total of eight full arcs; and a feet-first AP/PA plan with three isocenters that covers the lower extremities of the patient. PTV was the entire body cropped 5Â mm from the patient surface and extended 3Â mm into the lungs and kidneys. Two plans were generated for each case: one to a total dose of 1200Â cGy in 8 fractions and a second one to a total dose of 1320Â cGy in 8 fractions. Plans were calculated using the AAA algorithm and 6Â MV photon energy. One plan was created and delivered to an anthropomorphic phantom containing 12 OSLDs for in-vivo dose verification. For the plans prescribed to 1200Â cGy total dose the following dosimetric results were achieved: median PTV V100%Â =Â 94.5%; median PTV D98%Â =Â 89.9%; median lungs DmeanÂ =Â 763Â cGy; median left kidney DmeanÂ =Â 1058Â cGy; and median right kidney DmeanÂ =Â 1051Â cGy. For the plans prescribed to 1320Â cGy total dose the following dosimetric results were achieved: median PTV V100%Â =Â 95.0%; median PTV D98%Â =Â 88.7%; median lungs DmeanÂ =Â 798Â cGy; median left kidney DmeanÂ =Â 1059Â cGy; and median right kidney DmeanÂ =Â 1064Â cGy. Maximum dose objective was met for all cases. The dose deviation between the treatment planning dose and the dose measured by the OSLDs was within Â±4%. In summary, we have demonstrated that scripting can produce high-quality plans based on predefined dose objectives and can decrease planning time by automatic target and optimization contours generation, plan creation, field and isocenter placement, and optimization objectives setup.
Geometric Distortion Correction of Renal Diffusion Tensor Imaging Using the Reversed Gradient Method
ABSTRACT/UNASSIGNED:Renal echo planar diffusion tensor imaging (DTI) has clinical potential but suffers from geometric distortion. We evaluated feasibility of reversed gradient distortion correction in 10 diabetic patients and 6 volunteers. Renal area, apparent diffusion coefficient, fractional anisotropy, and tensor eigenvalues were measured on uncorrected and distortion-corrected DTI. Corrected DTI correlated better than uncorrected DTI (r = 0.904 vs 0.840, P = 0.002) with reference anatomic T2-weighted imaging, with no significant difference in DTI metrics.
Early Stage Pregnancy During Radiation Therapy to the Breast
We describe a model case of unplanned pregnancy during radiation therapy to the chest wall and peripheral lymphatics for breast cancer. We use the Morbidity and Mortality Conference format to demonstrate how radiation oncology departments should evaluate and manage this situation.
Full automation of spinal stereotactic radiosurgery and stereotactic body radiation therapy treatment planning using Varian Eclipse scripting
The purpose of this feasibility study is to develop a fully automated procedure capable of generating treatment plans with multiple fractionation schemes to improve speed, robustness, and standardization of plan quality. A fully automated script was implemented for spinal stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) plan generation using Eclipse v15.6 API. The script interface allows multiple dose/fractionation plan requests, planning target volume (PTV) expansions, as well as information regarding distance/overlap between spinal cord and targets to drive decision-making. For each requested plan, the script creates the course, plans, field arrangements, and automatically optimizes and calculates dose. The script was retrospectively applied to ten computed tomography (CT) scans of previous cervical, thoracic, and lumbar spine SBRT patients. Three plans were generated for each patient - simultaneous integrated boost (SIB) 1800/1600Â cGy to gross tumor volume (GTV)/PTV in one fraction; SIB 2700/2100Â cGy to GTV/PTV in three fractions; and 3000Â cGy to PTV in five fractions. Plan complexity and deliverability patient-specific quality assurance (QA) was performed using ArcCHECK with an Exradin A16 chamber inserted. Dose objectives were met for all organs at risk (OARs) for each treatment plan. Median target coverage was GTV V100%Â =Â 87.3%, clinical target volume (CTV) V100%Â =Â 95.7% and PTV V100%Â =Â 88.0% for single fraction plans; GTV V100%Â =Â 95.6, CTV V100%Â =Â 99.6% and PTV V100%Â =Â 97.2% for three fraction plans; and GTV V100%Â =Â 99.6%, CTV V100%Â =Â 99.1% and PTV V100%Â =Â 97.2% for five fraction plans. All plans (nÂ =Â 30) passed patient-specific QA (>90%) at 2%/2Â mm global gamma. A16 chamber dose measured at isocenter agreed with planned dose within 3% for all cases. Automatic planning for spine SRS/SBRT through scripting increases efficiency, standardizes plan quality and approach, and provides a tool for target coverage comparison of different fractionation schemes without the need for additional resources.